4-((4-(cyclohexylmethoxy)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)benzenesulfonamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-((4-(cyclohexylmethoxy)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)benzenesulfonamide
• 英文别名: 4-[[4-(cyclohexylmethoxy)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]amino]benzenesulfonamide
• 化学式: C₁₈H₂₂N₆O₃S
• 分子量: 402.477
• InChiKey: MWINFFOPTSOXJI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  144
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  环己甲醇 在 氯化亚砜 、 sodium hydride 、 三氟乙酸 、 lithium chloride 、 亚硝酸异戊酯 作用下， 以 2,2,2-三氟乙醇 、 N,N-二甲基乙酰胺 、 二甲基亚砜 为溶剂， 反应 43.0h， 生成 4-((4-(cyclohexylmethoxy)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)benzenesulfonamide
  参考文献：
  名称：

  Cyclin-Dependent Kinase (CDK) Inhibitors: Structure–Activity Relationships and Insights into the CDK-2 Selectivity of 6-Substituted 2-Arylaminopurines

  摘要：

  Purines and related heterocycles substituted at C-2 with 4'-sulfamoylanilino and at C-6 with a variety of groups have been synthesized with the aim of achieving selectivity of binding to CDK2 over CDK1. 6-Substituents that favor competitive inhibition at the ATP binding site of CDK2 were identified and typically exhibited 10-80-fold greater inhibition of CDK2 compared to CDK1. Most impressive was 44(6-([1,1'-bipheny1]-3-y1)-9H-purin-2-yl)amino) benzenesulfonamide (73) that exhibited high potency toward CDK2 (IC50 0.044 mu M) but was similar to 2000-fold less active toward CDK1 (IC50 86 mu M). This compound is therefore a useful tool for studies of cell cycle regulation. Crystal structures of inhibitor kinase complexes showed that the inhibitor stabilizes a glycine-rich loop conformation that shapes the ATP ribose binding pocket and that is preferred in CDK2 but has not been observed in CDK1. This aspect of the active site may be exploited for the design of inhibitors that distinguish between CDK1 and CDK2.

  DOI：

  10.1021/acs.jmedchem.6b01254

文献信息

• WO2008/39359
  申请人：——

  公开号：——

  公开（公告）日：——
• BICYCLIC PYRIMIDINE KINASE INHIBITORS
  申请人：Connolly Peter J.

  公开号：US20090076037A1

  公开（公告）日：2009-03-19

  The present invention is directed to novel bicyclic pyrimidine compounds of Formula (I) or a form or composition thereof and the use thereof as inhibitors of ATP-protein kinase interactions.
• US8314234B2
  申请人：——

  公开号：US8314234B2

  公开（公告）日：2012-11-20
• [EN] BICYCLIC PYRIMIDINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE PYRIMIDINE KINASE BICYCLIQUE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2008039359A2

  公开（公告）日：2008-04-03

  [EN] The present invention is directed to novel bicyclic pyrimidine compounds of Formula (I) or a form or composition thereof, and the use thereof as inhibitors of ATP-protein kinase interactions.
  [FR] La présente invention concerne des nouveaux composés de pyrimidine bicyclique de formule (I) ou leur forme ou composition, et leur utilisation en tant qu'inhibiteurs d'interactions avec l'ATP-protéine kinase.